Tissue-Resident Innate Immune Cell-Based Therapy: A Cornerstone of Immunotherapy Strategies for Cancer Treatment

Cancer immunotherapy has led to impressive advances in cancer treatment. Unfortunately, in a high percentage of patients is difficult to consistently restore immune responses to eradicate established tumors. It is well accepted that adaptive immune cells, such as B lymphocytes, CD4+ helper T lymphocytes, and CD8+ cytotoxic T-lymphocytes (CTLs), are the most effective cells able to eliminate tumors. However, it has been recently reported that innate immune cells, including natural killer cells (NK), dendritic cells (DC), macrophages, myeloid-derived suppressor cells (MDSCs), and innate lymphoid cells (ILCs), represent important contributors to modulating the tumor microenvironment and shaping the adaptive tumor response. In fact, their role as a bridge to adaptive immunity, make them an attractive therapeutic target for cancer treatment. Here, we provide a comprehensive overview of the pleiotropic role of tissue-resident innate immune cells in different tumor contexts. In addition, we discuss how current and future therapeutic approaches targeting innate immune cells sustain the adaptive immune system in order to improve the efficacy of current tumor immunotherapies

Seismic noise cross-correlation in the urban area of Benevento city (Southern Italy)

This article has been accepted for publication in Geophysical Journal International ©: The Authors 2019. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved. Uploaded in accordance with the publisher's self-archiving policy.In the last decade the use of passive methods has become appealing in reconstructing the properties of the propagation medium by seismic ambient noise data, without the use of localized natural or artificial sources. A temporary seismic network was installed in the urban area of Benevento (southern Italy) in order to characterize the shallow structure of the city using stable methods for the analysis of the seismic noise continuously acquired by stations. The city of Benevento is one of the italian areas with highest seismic hazard, and at present the region is affected by low energy swarms and sparse events (Ml ≤ 4.1). It has been struck by several destructive historical earthquakes, the strongest of which occurred in 1456, 1688, 1805 with associated MCS intensity up to X–XI. We used the sixteen seismic stations installed in Benevento to record ambient noise for about 1 month. The stations were equipped with different seismic instruments: (i) digitizers Quanterra Q330 connected to Le3d-5 s short-period sensors; (ii) Nanometrics Centaur digitizers coupled with Trillium Compact 120s broad-band velocimeters; (iii) one station with Episensor force balance accelerometer connected to a D6BB-DIN Staneo digitizer. Interstations Green's functions were reconstructed by the cross-correlation of continuous ambient noise data, and surface waves signals were extracted from Green's Functions (GFs) for investigating the elastic properties of the subsurface structure. In this regard, we performed the beamforming analysis to test the hypothesis of isotropy distribution of noise sources on which the cross-correlation method is based, and the particle motion analysis to confirm the presence of surface Rayleigh waves in the GFs. We analysed the temporal stability of the cross-correlated signals and the results show that 2 weeks of continuous measurements are sufficient to stabilize the surface waves signal extracted from the GFs. The phase velocity dispersion curves are computed for 115 station pairs through the use of a far-field representation of the surface-wave GFs and an image transformation technique. Our strategy based on cross-correlation analysis provides robust phase-velocity dispersion curves that vary approximately from 1.4 km s–1 at 0.7 Hz to 0.6 km s–1 at 5 Hz. Different pairs were selected for the inversion of phase-velocity dispersion curves aimed to derive 1-D shear-wave velocity (Vs) profiles (up to a maximum depth of about 500 m) representative of some areas of the city characterized by different soil deposits.Published1524–15425T. Sismologia, geofisica e geologia per l'ingegneria sismicaJCR Journa

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients

Toward highly potent cancer agents by modulating the c-2 group of the arylthioindole class of tubulin polymerization inhibitors

New arylthioindole derivatives having different cyclic substituents at position 2 of the indole were synthesized as anticancer agents. Several compounds inhibited tubulin polymerization at submicromolar concentration and inhibited cell growth at low nanomolar concentrations. Compounds 18 and 57 were superior to the previously synthesized 5. Compound 18 was exceptionally potent as an inhibitor of cell growth: it showed IC50 = 1.0 nM in MCF-7 cells, and it was uniformly active in the whole panel of cancer cells and superior to colchicine and combretastatin A-4. Compounds 18, 20, 55, and 57 were notably more potent than vinorelbine, vinblastine, and paclitaxel in the NCI/ADR-RES and Messa/Dx5 cell lines, which overexpress P-glycoprotein. Compounds 18 and 57 showed initial vascular disrupting effects in a tumor model of liver rhabdomyosarcomas at 15 mg/kg intravenous dosage. Derivative 18 showed water solubility and higher metabolic stability than 5 in human liver microsomes

Bytes from Ink/Ink from Bytes: the Complexity of Data from the Italian Archaeological Activities at Dahāne-ye Gholāmān, Qal‘a-ye Sam and Qal‘a-ye Tepe

In the autumn of 1959, IsMEO (Istituto per il Medio ed Estremo Oriente) started its archaeological activities in the eastern Iranian region of Sistan (1959-1978) with a survey carried out by its Founder and President, Prof. Giuseppe Tucci. After two preliminary campaigns (1960 and 1961), from 1962 the attention of the IsMEO focused on the site of Dahāne-ye Gholāmān, in the vicinity of the village called Qal‘a-ye Now, at about 30 km south-east from Zabul. There, the late Prof. Umberto Scerrato directed several seasons of excavations and restoration activities (1962-1965 and 1975-1977), revealing a huge complex of monumental buildings of a possible Achaemenian age (VI-IV century BC), which could have represented the main urban centre of ancient Drangiana and one of the few archaeologically documented sites on the Iranian Plateau for the Achaemenian period.\ud Beside the main archaeological activities at Dahāne-ye Gholāmān, the scientific interest of the IsMEO team headed by Prof. Scerrato was attracted by two other smaller sites. In 1961 and 1962 soundings were carried out at the fortified citadel of Qal‘a-ye Tepe (20 km north-east of Zabul), while in 1964 some trenches were carried out at the fortified citadel of Qal‘a-ye Sam (located some kilometres east of Dahāne-ye Gholāmān). Those activities had the aim to investigate the development both of the settlement pattern and the ceramic sequence during post-Achaemenian phases of the historical period (Seleucid, Parthian and Sasanian) in that are

Due ceramiche preistoriche/Two Prehistoric Pottery Vessels

Publication concerning two proto-historic pottery vessels from Iran presently stored at the Museo Orientale Umberto Scerrato in Naple

Pierfrancesco Callieri, Alireza Askari Chaverdi, Ali Eghraʿ, Diego Maria Mezzapelle, Kourosh Mohammadkhani. “The Dynamics of Human Settlement in Historical Times in South-Central Fars, from Firuzabad to the Persian Gulf: First Preliminary Results of a New Research Project”

Review of a paper on a multidisciplinary research project launched in 2019 within the frame of the long-established Iranian-Italian Joint Archaeological Mission in Fars